Maternal and neonatal characteristics in obstetric intensive care unit admissions.

BACKGROUND: The objective of this study was to evaluate the course of pregnancy and delivery of obstetric patients admitted for intensive care, and determine the health status of their infants. METHODS: This was a retrospective register-based study. Four university hospitals in Finland participated. Obstetric patients admitted to the intensive care unit in any trimester of pregnancy, during delivery or up to 42 days post partum were identified from clinical information systems over a five-year study period. Parturient and infant data were collected from the Medical Birth Register. RESULTS: During the study period (2007-2011), 283 obstetric patients were identified from the clinical information system. The most common reason for admission was hypertensive complications (58%), followed by obstetric haemorrhage (25.1%). Advanced maternal age, nulliparity and multiple pregnancies were associated with obstetric intensive care unit admissions. Of patients admitted to intensive care, 68.9% delivered by unscheduled caesarean section. Nearly 60% of neonates were born preterm, 56.1% needed treatment in a neonatal intensive care unit or an observation unit and 4.6% died within one week. CONCLUSION: Advanced maternal age, nulliparity and multiple pregnancy were more common among intensive care unit-admitted women than in the general obstetric population. The main causes for admission were hypertensive complications and obstetric haemorrhage. Compared with the general obstetric population, neonates of intensive care unit-admitted mothers were eight times more likely to require treatment on a neonatal ward and their risk of neonatal death was also eight times greater.

Workplace culture assessed by radiographers in Finland.

INTRODUCTION: The purpose of this study was to describe workplace culture from the radiographers' point of view. METHODS: Data collection was carried out in 2017 using a structured electronic survey in Finland. The target population were radiographers of working age (N = 1808) - response rate 38% (n = 689). The questionnaire included background questions and The Nursing Context Index -instrument developed by Slater and McCormack. Workplace culture is described in the domains of work-related stress (36 items), job satisfaction (18 items), and practice environment (24 items). The respondents rated their level of agreement to statements on a seven-degree Likert-scale. Data analysis was performed using SPSS 24 -software. RESULTS: The results show that radiographers saw their workplace culture as slightly positive. They experienced some degree of stress caused mostly by workload, and least stress in relation to their career development. Radiographers were fairly satisfied in their work, with personal satisfaction featuring as the highest rated area of satisfaction, and pay and prospects as the lowest. The practice environment was perceived slightly positively. Radiographers wanted to stay in their current jobs, but felt that they had only a small degree of control over their work. CONCLUSIONS: According to this study, workplace culture is experienced by radiographers on a moderate and slightly positive level. Because workplace culture is connected to quality of care and staff's work and organizational results, it is important to improve the culture that radiographers encounter, so as to create a healthy work community that offers productive and high-quality healthcare to patients.

Effects of a 20-week high-intensity strength and sprint training program on tibial bone structure and strength in middle-aged and older male sprint athletes: a randomized controlled trial.

This randomized, controlled, high-intensity strength and sprint training trial in middle-aged and older male sprint athletes showed significant improvements in mid-tibial structure and strength. The study reveals the adaptability of aging bone, suggesting that through a novel, intensive training stimulus it is possible to strengthen bones during aging. INTRODUCTION: High-load, high-speed and impact-type exercise may be an efficient way of improving bone strength even in old age. We evaluated the effects of combined strength and sprint training on indices of bone health in competitive masters athletes, who serve as a group of older people who are likely to be able to participate in vigorous exercise of this kind. METHODS: Seventy-two men (age 40-85) were randomized into an experimental (EX, n = 40) and a control (CTRL, n = 32) group. EX participated in a 20-week program combining heavy and explosive strength exercises with sprint training. CTRL maintained their usual, run-based sprint training schedules. Bone structural, strength and densitometric parameters were assessed by peripheral QCT at the distal tibia and tibial midshaft. RESULTS: The intervention had no effects on distal tibia bone traits. At the mid-tibia, the mean difference in the change in cortical thickness (ThCO) in EX compared to CTRL was 2.0% (p = 0.007). The changes in structure and strength were more pronounced in the most compliant athletes (training adherence >75%). Compared to CTRL, total and cortical cross-sectional area, ThCO, and the area and density-weighted moments of inertia for the direction of the smallest flexural rigidity (I minA , I minD ) increased in EX by 1.6-3.2% (p = 0.023-0.006). Polar mass distribution analysis revealed increased BMC at the anteromedial site, whereas vBMD decreased (p = 0.035-0.043). CONCLUSIONS: Intensive strength and sprint training improves mid-tibia structure and strength in middle-aged and older male sprint athletes, suggesting that in the presence of high-intensity loading exercise, the adaptability of the bone structure is maintained during aging.

Workplace culture in psychiatric nursing described by nurses.

AIM: This study looks to describe the workplace culture from the viewpoints of stress, job satisfaction and practice environment. METHODS: Data were collected from nurses (n = 109) using a web-based survey, The Person-Centred Nursing Index, from two purposefully selected hospital districts in Finland. Data were statistically analysed. RESULTS: Nurses described their workplace culture in slightly positive terms. Nurses only occasionally experienced stress (mean = 2.56, SD = 0.55) and were fairly satisfied with their job (mean = 4.75, SD = 0.66) and their practice environment (mean = 4.42, SD = 0.81). Demographic variables such as the nurses' age, length of time in nursing, time at their present hospital, working shifts and their use of patient restriction were more frequently associated with their perceived workplace culture. CONCLUSION: Older nurses and those with a longer work history in the nursing profession tended to be more satisfied with their workplace culture in psychiatric nursing. Young and/or newly graduated nurses felt more negatively on their workplace culture; this issue should be recognised and addressed with appropriate support and mentoring. Nurses who used restrictive measures were more often less satisfied with their workplace culture. Continuous efforts are needed to reduce the use of coercive measures, which challenge also the managers to support nursing practice to be more person-centred.

Stigmatizing attitudes in nurses towards people with mental illness: a cross-sectional study in primary settings in Finland.

WHAT IS KNOWN ON THE SUBJECT?: Stigma related to mental illnesses is a great burden on societies globally. Factors associated with nurses' attitudes towards people with mental illness in health-care settings are discrepant. Stigmatized attitudes among staff members towards patients with mental illness have widely been studied in various specialized health care contexts, but less often in primary health-care settings. WHAT THIS PAPER ADDS TO THE EXISTING KNOWLEDGE?: Nurses' attitudes towards people with mental illness in general were positive in primary care health settings. Younger nurses expressed feeling afraid of mentally ill patients. They not only lacked a feeling of safety around these patients but were also often of the opinion that people with mental illness should be segregated from the general population. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Systematic and continuous mental health on-the-job training for primary care nurses is recommended to strengthen the positive attitudes of young nurses towards patients. Young nurses especially should be prevented from developing stigmatized attitudes towards patients with mental problems and to ensure a skilled workforce for the future in this demanding area of health care. ABSTRACT: Introduction Despite the development of mental health services in many countries, nurses working in different health care specialties may still have concerns and negative attitudes towards people with mental illness. Aim To describe nurses' attitudes towards people with mental illness and examine factors associated with their attitudes in primary care health centres. Method The data were collected from nursing staff (N = 264, response rate 84%) in 15 primary care health centres in two Finnish cities (spring 2014) with a self-report questionnaire (Attribution Questionnaire-27, Corrigan 2003) and analysed by descriptive statistics and multiway covariance analysis. Results Nurses' attitudes towards people with mental illness were generally positive. The nurses mostly reported willingness to help and feelings of concern and sympathy towards these patients. However, younger nurses or those without additional mental health training expressed a fear of patients. Discussion Special attention should be paid to nursing education and on-the-job training to prevent young nurses from developing stigmatized attitudes towards patients. Implications for practice Higher confidence in nursing staff could ensure a skilled work force in areas of mental health in the future, prevent young nurses from developing a fear of patients at work and support positive attitudes towards patients with mental problems.

What does caring mean to nursing and social work students?

AIM: The aim of this study in Lithuania was to discover how the meaning of caring is perceived by nursing and social work students. BACKGROUND: Nursing and social work are caring professions, which provide care in different ways. It is still unclear what features constitute the meaning of caring for nursing and social work students as future caring professionals. METHODS: Snowball sampling technique was applied in the study. The data were collected as reflective narratives. Data were analysed using qualitative content analysis. FINDINGS: For nursing and social work students, the meaning of caring comprises mission, proficiency, values and collaboration. These features overlap, but the implementation of caring is dependent on the particular profession. DISCUSSION: Nursing and social work students describe the meaning of caring as holistic assistance to patient/client: the work mission for both. However, the tasks, responsibilities and focus on providing care to a patient/client differ in both professions. LIMITATIONS: Reflective narratives were preferred to semi-structured interviews. The researchers did not contact the participants in person to ask them additional questions. CONCLUSION: The meaning of caring is perceived as a developmental phenomenon, which depends on professional philosophy, practice, continuing learning and experience. Nursing and social work students perceive it as a way of thinking about the individual's being in a profession and acting collaboratively for the wellbeing of others. IMPLICATIONS FOR HEALTH POLICY: Focus on the meaning of caring in nursing and social work (post)graduate education is a premise to shift the training from self- to other-centred, from mono- to multi-disciplinary approach. This is related to the shift of practices towards effective patient-centred team-working within the health system, with the spotlight on caring.

Nurses' perceptions of workplace culture in primary health care in Finland.

AIM: This study aimed to describe nurses' perceptions of workplace culture, especially in regard to stress levels, job satisfaction and the practice environment in primary health care. BACKGROUND: Health care is facing many challenges related to its attractiveness as a place of employment and the maintenance of a sufficient workforce supply. Previous studies report increasing rates of nurse job dissatisfaction and intentions to leave their current positions both in Finland and also globally. Improving workplace culture is thus vital in meeting the challenges related to recruitment and retention. METHODS: A cross-sectional descriptive design was used to describe nurses' perceptions of workplace culture. Data were collected by questionnaire from 22 units in nine primary healthcare organizations in Finland, and analysed using descriptive and inferential statistics. RESULTS: Most of the respondents indicated that they were not certain whether their workplace culture was either positive or negative. Profession, age and work shift characteristics had an effect on the respondents' perceptions of workplace culture. Younger licensed practical and registered nurses assessed their workplace culture more positively, whereas older registered nurses and those working rotating rosters viewed workplace culture more negatively. CONCLUSIONS: The findings suggest that both unit and demographic characteristics affect workplace culture. This survey highlights that a positive workplace culture is one of the key factors in retaining and recruiting nurses, and provides an essential evidence that may be considered by other healthcare organizations. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse managers and healthcare leaders need to address workload management and take into account the related variables that affect a unit's workplace culture.

REASONS AND CONSEQUENCES OF APPLIED LEADERSHIP STYLES IN ETHICAL DILEMMAS WHEN NURSE MANAGERS MAKE DECISIONS.

Abstract Background: Understanding the reasons and consequences of leadership styles in ethical dilemmas is fundamental to exploring nurse managers' abilities to influence outcomes for patients and nursing personnel. Purpose: To explain the associations between different leadership styles, reasons for their application and its consequences when nurse managers make decisions in ethical dilemmas. Methods: The data were collected between 15 October 2011 and 30 April 2012 by statistically validated questionnaire. The respondents (n=278) were nurse managers. The data were analyzed using SPSS 20.0, calculating Spearman's correlations, the Stepwise Regression and ANOVA. Results: The reasons for applying different leadership styles in ethical dilemmas include personal characteristics, years in work position, institutional factors, and the professional authority of nurse managers. The applied leadership styles in ethical dilemmas are associated with the consequences regarding the satisfaction of patients', relatives' and nurse managers' needs. Conclusions: Nurse managers exhibited leadership styles oriented to maintenance, focusing more on the "doing the job" than on managing the decision-making in ethical dilemmas.

Hospital nurses' individual priorities, internal psychological states and work motivation.

AIM: This study looks to describe the relationships between hospital nurses' individual priorities, internal psychological states and their work motivation. BACKGROUND: Connections between hospital nurses' work-related needs, values and work motivation are essential for providing safe and high quality health care. However, there is insufficient empirical knowledge concerning these connections for the practice development. METHODS: A cross-sectional empirical research study was undertaken. A total of 201 registered nurses from all types of Estonian hospitals filled out an electronic self-reported questionnaire. Descriptive statistics, Mann-Whitney, Kruskal-Wallis and Spearman's correlation were used for data analysis. RESULTS: In individual priorities, higher order needs strength were negatively correlated with age and duration of service. Regarding nurses' internal psychological states, central hospital nurses had less sense of meaningfulness of work. Nurses' individual priorities (i.e. their higher order needs strength and shared values with the organization) correlated with their work motivation. Their internal psychological states (i.e. their experienced meaningfulness of work, experienced responsibility for work outcomes and their knowledge of results) correlated with intrinsic work motivation. DISCUSSION: Nurses who prioritize their higher order needs are more motivated to work. The more their own values are compatible with those of the organization, the more intrinsically motivated they are likely to be. CONCLUSION: Nurses' individual achievements, autonomy and training are key factors which influence their motivation to work. LIMITATIONS: The small sample size and low response rate of the study limit the direct transferability of the findings to the wider nurse population, so further research is needed. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study highlights the need and importance to support nurses' professional development and self-determination, in order to develop and retain motivated nurses. It also indicates a need to value both nurses and nursing in healthcare policy and management.

Leadership styles in ethical dilemmas when head nurses make decisions.

BACKGROUND: The overlooked aspect in Lithuania is the dearth of leaders among head nurses, who bear the responsibility for decisions in ethical dilemmas. Understanding the application of leadership styles is fundamental to ensuring head nurses' abilities to influence outcomes for healthcare providers and patients. AIM: To identify the leadership styles applied by head nurses in decision making in ethical dilemmas on hospital wards. METHODS: The data were collected by questionnaires completed by head nurses (n = 278) working in five major state-funded hospitals in each of the five regions of Lithuania. The data were analysed using SPSS 16.0, calculating descriptive statistics and analysis of variance. FINDINGS: Head nurses apply democratic, affiliative, transformational and sustainable leadership styles when resolving ethical dilemmas. The application of leadership styles is associated not only with specific situations, but also with certain background factors, such as years of experience in a head nurse's position, ward specialization and the incidence of ethical dilemmas. Nurses having been in a head nurse's position over 10 years use primitive leadership styles, notably bureaucratic leadership, more often than do those head nurses with only a few years of experience in such a position. CONCLUSIONS: The results highlight the need for head nurses to reflect on their practices and to find new ways of learning from practice, colleagues and patients. Head nurses' managerial decisions due to their 'executive power' can turn into a new state-of-the-art leadership in nursing.

Motives of cancer patients for using the Internet to seek social support.

The purpose of the study was to describe why Finnish cancer patients choose the internet as a source of social support. The data were collected in May 2010, using an online questionnaire with open-ended questions, through four discussion forums on the websites of the non-profit Cancer Society of Finland. Seventy-four adult patients with cancer participated. The data were analysed using inductive content analysis. The mean age of the participants was 53 years and they were predominantly women. The most common cancer was breast cancer and more than three quarters of the participants had suffered from cancer for less than 5 years. The initial stimuli to use the internet as a source of social support were the ease of communication and access to information as well as the need for emotional and informational support. The actual motives that drove the use of the internet as a source of social support were the requirements for information and peer support, internet technology, a lack of support outside the internet and the negative experiences caused by the illness. The fact that there is an enormous need for information as well as for emotional support and that cancer treatment in Finland is concentrated in major hospitals, to which cancer patients may travel a considerable distance, suggests that nurses should learn to make more frequent virtual contact with their patients.

Altered expression and splicing of Ca(2+) metabolism genes in myotonic dystrophies DM1 and DM2.

AIMS: Myotonic dystrophy types 1 and 2 (DM1 and DM2) are multisystem disorders caused by similar repeat expansion mutations, with similar yet distinct clinical features. Aberrant splicing of multiple effector genes, as well as dysregulation of transcription and translation, has been suggested to underlie different aspects of the complex phenotypes in DM1 and DM2. Ca(2+) plays a central role in both muscle contraction and control of gene expression, and recent expression profiling studies have indicated major perturbations of the Ca(2+) signalling pathways in DM. Here we have further investigated the expression of genes and proteins involved in Ca(2+) metabolism in DM patients, including Ca(2+) channels and Ca(2+) binding proteins. METHODS: We used patient muscle biopsies to analyse mRNA expression and splicing of genes by microarray expression profiling and RT-PCR. We studied protein expression by immunohistochemistry and immunoblotting. RESULTS: Most of the genes studied showed mRNA up-regulation in expression profiling. When analysed by immunohistochemistry the Ca(2+) release channel ryanodine receptor was reduced in DM1 and DM2, as was calsequestrin 2, a sarcoplasmic reticulum lumen Ca(2+) storage protein. Abnormal splicing of ATP2A1 was more pronounced in DM2 than DM1. CONCLUSIONS: We observed abnormal mRNA and protein expression in DM affecting several proteins involved in Ca(2+) metabolism, with some differences between DM1 and DM2. Our protein expression studies are suggestive of a post-transcriptional defect(s) in the myotonic dystrophies.

Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5.

OBJECTIVE: Description of 8 new ANO5 mutations and significant expansion of the clinical phenotype spectrum associated with previously known and unknown mutations to improve diagnostic accuracy. METHODS: DNA samples of 101 patients in 95 kindreds at our quaternary referral center in Finland, who had undetermined limb-girdle muscular dystrophy (LGMD), calf distal myopathy, or creatine kinase (CK) elevations of more than 2,000 IU/L, were selected for ANO5 genetic evaluation, and the clinical findings of patients with mutations were retrospectively analyzed. RESULTS: A total of 25 patients with muscular dystrophy caused by 11 different recessive mutations in the ANO5 gene were identified. The vast majority of mutations, 8 of 11, proved to be previously unknown new mutations. The most frequent mutation, c.2272C>T (p.R758C), was present in 20 patients. The phenotypes associated with this and the common European mutation, c.191dupA, varied from nearly asymptomatic high hyperCKemia to severe LGMD with consistently milder phenotypes in female patients. CONCLUSIONS: Mutations in ANO5 are a frequent cause of undetermined muscular dystrophy, with both distal and proximal presentation. Other types include high hyperCKemia, myalgia, or calf hypertrophy over decades without significant weakness, especially in female patients. Mutations are distributed all over the gene, indicating that muscular dystrophy caused by ANO5 can be expected to occur in all populations.

Spanish MYH7 founder mutation of Italian ancestry causing a large cluster of Laing myopathy patients.

Laing myopathy is a distal myopathy caused by mutations in the tail of the slow beta-myosin heavy chain gene MYH7. A large cluster of patients belonging to different families, with Laing myopathy due to p.K1729del mutation, was found in the Safor region, Spain. The same mutation was previously reported in an American family with Italian ancestry. The possibility that p.K1729del in MYH7 might be a founder mutation in the Safor patients and the chance of a common origin with the Italian-American family mutation was investigated by haplotype analyses, mutation data origin estimation and historical inquiry. Our results show that the p.K1729del in MYH7 harboured by patients from the Safor indeed is a founder mutation. A common ancestral origin of this mutation in the Spanish and Italian families is also suggested because they all share a core SNP haplotype at locus MYH7. Data estimation yields the origin of the mutation in the Safor at the beginning of the XVII century, when the Moorish were spelt and the region was resettled with Italian families.

Outcomes assessment of the regional health information exchange: a five-year follow-up study.

BACKGROUND: The implementation of a technology such as health information exchange (HIE) through a Regional Health Information System (RHIS) may improve the mobilization of health care information electronically across organizations. There is a need to coordinate care and bring together regional and local stakeholders. OBJECTIVES: To describe how HIE had influenced health care delivery in one hospital district area in Finland. METHOD: Trend analysis was used to evaluate the influence of a regional HIE. We conducted a retrospective, longitudinal study for the period 2004-2008 for the eleven federations of municipalities in the study area. We reviewed statistical health data from the time of implementation of an RHIS. The t-test was used to determine statistical significance. The selected outcomes were the data obtained from the regional database on total appointments, emergency department visits, laboratory tests and radiology examinations, and selected laboratory tests and radiology examinations carried out in both primary care and special health care. RESULTS: Access to HIE may have influenced health care delivery in the study area. There are indications that there is a connection between access to regional HIE and the number of laboratory tests and radiology examinations performed in both primary care and specialized health care, as observed in the decreased frequency in outcomes such as radiology examinations, number of appointments, and emergency department visits in the study environment. The decreased frequencies of the latter suggest an increased efficiency of outpatient care, but we were not able to estimate to what extent the readily available comprehensive clinical information contributed to these trends. CONCLUSION: Outcome assessment of HIE through an RHIS is essential for the success of health information technology (HIT) and as evidence to use in the decision-making process. As health care information becomes more digital, it increases the potential for a strong HIE effect on health care delivery.

MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy.

OBJECTIVE: To describe a wide range of clinical and pathologic myopathic profiles associated with the p.K1729del mutation in the MYH7 gene, known to cause Laing distal myopathy. METHODS: A study conducted in the Safor region (Spain), setting of a large cluster of patients. Clinical, neurophysiologic, muscle imaging, and muscle biopsy studies and MYH7 gene sequencing were investigated in 32 patients from 4 kindreds. Data from 36 deceased or nonexamined patients were collected from hospital records or relatives. RESULTS: Onset ranged from congenital to the 6th decade. All patients presented weakness of great toe/ankle dorsiflexors and many had associated neck flexor, finger extensor, and mild facial weakness. In most cases, involvement of proximal and axial muscles was observed either clinically or by muscle imaging, sometimes giving rise to scapuloperoneal and limb-girdle syndromes. Disabling myalgias, skeletal deformities, and dilated cardiomyopathy in one patient were associated features. Life expectancy was not reduced but the spectrum of disability ranged from asymptomatic to wheelchair confined. Electromyographic neurogenic features were frequently recorded. Muscle fiber type disproportion, core/minicore lesions, and mitochondrial abnormalities were the most relevant pathologic alterations. All patients carried the p.K1729del mutation in MYH7. CONCLUSIONS: The p.K1729del mutation in the MYH7 gene expresses notable clinical variability and electromyographic and pathologic features that can lead to the misdiagnosis of neurogenic atrophies, congenital myopathies, or mitochondrial myopathies. Mutations in genes encoding other sarcomeric and reticulo-sarcoplasmic proteins involved in calcium regulation share pathologic characteristics with our patients, suggesting a possible pathogenetic connection.

Myopathies caused by homozygous titin mutations: limb-girdle muscular dystrophy 2J and variations of phenotype.

Limb-girdle muscular dystrophy 2J caused by mutations in C-terminal titin has so far been identified in Finnish patients only. This may in part be due to limited availability of diagnostic tests for titin defects. In this report, a French family with an autosomal-dominant late-onset distal myopathy of the tibial muscular dystrophy phenotype segregating in several members of the family was described. One deceased patient in the family proved to be homozygous for the C-terminal truncating titin mutation because of consanguinity. According to available medical records, the patient had a clearly more severe generalised muscle weakness and atrophy phenotype not recognised as a distal myopathy at the time. Autopsy findings in one of the original Finnish limb-girdle muscular dystrophy 2J patients were reported and the early phenotype in a newly identified young patient with homozygous Finnish C-terminal titin mutation (FINmaj) was detailed.

Identification of free and conjugated metabolites of mesocarb in human urine by LC-MS/MS.

The objective of the present study was to investigate mesocarb metabolism in humans. Samples obtained after administration of mesocarb to healthy volunteers were studied. The samples were extracted at alkaline pH using ethyl acetate and salting-out effect to recover metabolites excreted free and conjugated with sulfate. A complementary procedure was applied to recover conjugates with glucuronic acid or with sulfate consisting of the extraction of the urines with XAD-2 columns previously conditioned with methanol and deionized water; the columns were then washed with water and finally eluted with methanol. In both cases, the dried extracts were reconstituted and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Chromatographic separation was carried out using a C(18) column (100 mm x 2.1 mm i.d., 1.7 microm particle size) and a mobile phase consisting of water and acetonitrile with 0.01% formic acid with gradient elution. The chromatographic system was coupled to a mass spectrometer with an electrospray ionization source working in positive mode. Metabolic experiments were performed in multiple-reaction monitoring mode by monitoring one transition for each potential mesocarb metabolite. Mesocarb and 19 metabolites were identified in human urine, including mono-, di-, and trihydroxylated metabolites excreted free as well as conjugated with sulfate or glucuronic acid. All metabolites were detected up to 48 h after administration. The structures of most metabolites were proposed based on data from reference standards available and molecular mass and product ion mass spectra of the peaks detected. The direct detection of mesocarb metabolites conjugated with sulfate and glucuronic acid without previous hydrolysis has been described for the first time. Finally, a screening method to detect the administration of mesocarb in routine antidoping control analyses was proposed and validated based on the detection of the main mesocarb metabolites in human urine (p-hydroxymesocarb and p-hydroxymesocarb sulfate). After analysis of several blank urines, the method demonstrated to be specific. Extraction recoveries of 100.3 +/- 0.8 and 105.9 +/- 10.8 (n = 4), and limits of detection of 0.5 and 0.1 ng mL(-1) were obtained for p-hydroxymesocarb sulfate and p-hydroxymesocarb, respectively. The intra- and inter-assay precisions were estimated at two concentration levels, 50 and 250 ng mL(-1), and relative standard deviations were lower than 15% in all cases (n = 4).

Premutation allele pool in myotonic dystrophy type 2.

BACKGROUND: The myotonic dystrophies (DM1, DM2) are the most common adult muscle diseases and are characterized by multisystem involvement. DM1 has been described in diverse populations, whereas DM2 seems to occur primarily in European Caucasians. Both are caused by the expression of expanded microsatellite repeats. In DM1, there is a reservoir of premutation alleles; however, there have been no reported premutation alleles for DM2. The (CCTG)(DM2) expansion is part of a complex polymorphic repeat tract of the form (TG)(n)(TCTG)(n)(CCTG)(n)(NCTG)(n)(CCTG)(n). Expansions are as large as 40 kb, with the expanded (CCTG)(n) motif uninterrupted. Reported normal alleles have up to (CCTG)(26) with one or more interruptions. METHODS: To identify and characterize potential DM2 premutation alleles, we cloned and sequenced 43 alleles from 23 individuals. Uninterrupted alleles were identified, and their instability was confirmed by small-pool PCR. We determined the genotype of a nearby single nucleotide polymorphism (rs1871922) known to be in linkage disequilibrium with the DM2 mutation. RESULTS: We identified three classes of large non-DM2 repeat alleles: 1) up to (CCTG)(24) with two interruptions, 2) up to (CCTG)(32) with up to four interruptions, and 3) uninterrupted (CCTG)(22-33). Large non-DM2 alleles were more common in African Americans than in European Caucasians. Uninterrupted alleles were significantly more unstable than interrupted alleles (p = 10(-4) to 10(-7)). Genotypes at rs1871922 were consistent with the hypothesis that all large alleles occur on the same haplotype as the DM2 expansion. CONCLUSIONS: We conclude that unstable uninterrupted (CCTG)(22-33) alleles represent a premutation allele pool for DM2 full mutations.